PHYSIOLOGICAL-EFFECTS OF EXTRACELLULAR-SUPEROXIDE DISMUTASE TRANSGENEOVEREXPRESSION ON MYOCARDIAL-FUNCTION AFTER ISCHEMIA AND REPERFUSION INJURY

Objective: Myocardial injury after ischemia and reperfusion may be med iated, in part, by oxygen-derived free radicals. In this study the pro tective effects of extracellular superoxide dismutase overexpression w ere directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine hear t preparation and computerized analysis of functional data. Methods: A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, cont ractility, heart rate, stroke work, and stroke volume were evaluated i n the two groups before and after a 6-minute period of normothermic is chemia. Results: No differences were found between extracellular super oxide dismutase hearts and control hearts in any parameter of myocardi al function before ischemia. After ischemia, decreases in cardiac outp ut occurred in both groups; however, this decrease was larger in contr ol mice compared with extracellular superoxide dismutase mice. A highe r percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dism utase hearts compared with control hearts, Conclusion: After global no rmothermic ischemia and subsequent reperfusion, decreases in cardiac f unction occurred in both extracellular superoxide dismutase and contro l mice; however, a higher percentage of recovery was observed in the e xtracellular superoxide dismutase overexpressed hearts, These data sug gest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial Function after ische mia and reperfusion injury.